ArticleJournal of diabetes investigation2021
The PKM2 activator TEPP-46 suppresses kidney fibrosis via inhibition of the EMT program and aberrant glycolysis associated with suppression of HIF-1α accumulation.
Article in Journal of diabetes investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 101 citations in OpenAlex.
- circCACNA1D drives pulmonary fibrosis by regulating pyruvate kinase M2 dimer‑tetramer switching.International journal of molecular medicine · 2026Article
- Antifibrotic Effects of Yi-Qi-Jian-Pi-Xiao-Yu Formula in Kidney via HIF1A-Driven M1 Macrophage Polarization.Phytochemical analysis : PCA · 2026Article
- Review
- Unveiling lactylation: A novel frontier in the pathogenesis of diabetic nephropathy (Review).International journal of molecular medicine · 2026Review
- Glycolytic lactylation modulates cell death decisions in diabetic kidney disease: Metabolic‑epigenetic interplay between ferroptosis and autophagy in fibrotic remodeling (Review).International journal of molecular medicine · 2026Review
- PKM2-Mediated Glycolytic Reprogramming in Thyroid Cancer: Mechanistic Insights and Therapeutic Potential.Molecules (Basel, Switzerland) · 2026Review
- Ferroptosis-driven metabolic reprogramming in macrophages: Reshaping glucose utilization landscapes.Chinese medical journal · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- The biology of PKM2 in the metabolism and senescence in diabetic kidney disease.Journal of diabetes investigation · 2026Review
- High Glycolysis and Lipid Metabolism Status Predicts Poor Prognosis in Colorectal Cancer Patients.Current molecular medicine · 2026Article
- Nuclear translocation of pyruvate kinase M2 drives high glucose-induced angiogenesis in retinal endothelial cellsInternational journal of ophthalmology · 2026Article
- Pyruvate kinase M2 is elevated in systemic sclerosis and plays a role in its pathogenesis.Frontiers in immunology · 2026Article
- PKM2 mediates the glycolytic response to matrix stiffness in lung fibroblasts.Frontiers in cell and developmental biology · 2026Article
- Performance of novel biomarkers for prediction of diabetic kidney disease in patients with diabetes mellitus.Annals of medicine · 2025Observational
- Glycolysis to lactylation: Unraveling the metabolic and epigenetic landscape in tissue fibrosis (Review).Molecular medicine reports · 2025Review
- SGLT2 inhibition protects kidney function by SAM-dependent epigenetic repression of inflammatory genes under metabolic stress.The Journal of clinical investigation · 2025Article
- Dihydroartemisinin ameliorates renal tubulointerstitial fibrosis in diabetic nephropathy via restoring mitochondrial function via HIF-1α/HO-1 pathway.Scientific reports · 2025Article
- Pyruvate Kinase M2 Links Metabolism and Epigenetics: A New Target for Liver Disease Treatment.Biomolecules · 2025Review
- Autophagy-induced NR2F1 activation promotes the apoptosis of lens epithelial cells and facilitates cataract-associated fibrosis through targeting STAT3.Genes & diseases · 2025Article
- Lactate and lactylation in the kidneys: Current advances and prospects (Review).International journal of molecular medicine · 2025Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
AIMS/
introductionTubulointerstitial fibrosis is a hallmark of diabetic nephropathy and is associated with an epithelial-to-mesenchymal transition (EMT) program and aberrant glycolysis. Dimeric pyruvate kinase (PK) M2 (PKM2) acts as a key protein kinase in aberrant glycolysis by promoting the accumulation of hypoxia-inducible factor (HIF)-1α, while tetrameric PKM2 functions as a pyruvate kinase in oxidative phosphorylation. The aim of the research is to study the effect of PKM2 tetramer activation on preventing kidney fibrosis via suppression of aberrant glycolysis and the EMT program. MATERIALS AND
methodsIn vivo: Streptozotocin (STZ) was utilized to induce diabetes in 8-week-old CD-1 mice; 4 weeks after diabetes induction, proteinuria-induced kidney fibrosis was developed by intraperitoneal injection of bovine serum albumin (BSA: 0.3 g/30 g BW) for 14 days; The PKM2 activator TEPP-46 was also administered orally simultaneously. In vitro: HK2 cells were co-treated with high-glucose media or/and TGF-β1 and TEPP46 for 48 h, cellular protein was extracted for evaluation.
resultsDiabetic mice developed kidney fibrosis associated with aberrant glycolysis and EMT; BSA injection accelerated kidney fibrosis in both the control and diabetic mice; TEPP-46 rescued the kidney fibrosis. In HK2 cells, TEPP-46 suppressed the EMT program induced by TGF-β1 and/or high-glucose incubation. TEPP-46-induced PKM2 tetramer formation and PK activity resulted in suppression of HIF-1α and lactate accumulation. Specific siRNA-mediated knockdown of HIF-1α expression diminished high glucose-induced mesenchymal protein levels.
conclusionPKM2 activation could restore the tubular phenotype via suppression of the EMT program and aberrant glycolysis, providing an alternative target to mitigate fibrosis in diabetic kidneys.
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